Setting individuals with the lowest P% of phenotypes as cases and all other as controls generated dichotomous phenotypes with prevalence P. The small number of individuals prevented simulation of case-control ascertainment, which may produce downward bias for low prevalence diseases in very large studies (see Supplementary Table 9 in [19]). Those biases are expected to be small in the prostate cancer data analyzed here because of the high prevalence of prostate cancer and moderate sample size. For large sample sizes, replacing mixed model based estimates with Haseman-Elston regression estimates will alleviate the issue of ascertainment bias20.
